Background: The etiology and pathomechanism of schizophrenia are unknown. The traditional dopamine (DA) hypothesis is unable to fully explain its pathology and therapeutics. The glutamate (Glu) and γ-aminobutyric acid (GABA) hypotheses suggest Glu or GABA concentrations are abnormal in the brains of patients with schizophrenia. Magnetic resonance spectroscopy (MRS) show glutamate level increases in the ventromedial prefrontal cortex (vmPFC) including the anterior cingulated cortex (ACC) in those with schizophrenia...

Background: Several clinical studies have suggested that N-acetylaspartate and N-acetylaspartylglutamate levels in the human brain are associated with various psychiatric disorders, including major depressive disorder. We have previously identified Shati/Nat8l, an N-acetyltransferase, in the brain using an animal model of psychosis. Shati/Nat8l synthesizes N-acetylaspartate from L-aspartate and acetyl-coenzyme A. Further, N-acetylaspartate is converted into N-acetylaspartylglutamate, a neurotransmitter for metabotropic glutamate receptor 3...

Two spectral editing techniques for the simultaneous detection of glutathione (GSH) and lactate (Lac) in the human brain at 3 T are described and evaluated. These methods, 'sMEGA' (sinc-MEscher and GArwood) and 'DEW' (Double Editing With), were optimized to detect GSH and Lac simultaneously at 3 T using density-matrix simulations and validation in phantoms. Simulations to test for co-edited metabolites within the detected GSH region of the spectrum were also performed. In vivo data were acquired in the midline parietal region of seven subjects using both methods, and compared with conventional MEGA-PRESS (MEscher and GArwood-Point RESolved Spectroscopy) acquisitions of GSH and Lac...

Proton magnetic resonance spectroscopy ((1) H-MRS) can be used to quantify in vivo metabolite levels, such as lactate, γ-aminobutyric acid (GABA) and glutamate (Glu). However, there are considerable analysis choices which can alter the accuracy or precision of (1) H-MRS metabolite quantification. It is currently unknown to what extent variations in the analysis pipeline used to quantify (1) H-MRS data affect outcomes. The purpose of this study was to evaluate whether the quantification of identical (1) H-MRS scans across independent and experienced research groups would yield comparable results...

Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a protein complex involved in the formation of endosomal tubular structures that mediates the sorting of protein cargoes to specialised compartments. In this study, we present insights into the metabolic consequences caused by BLOC-1 deficiency in pallid mice, which carry a null mutation in the Bloc1s6 gene encoding an essential component of this complex. The metabolome of the hippocampus of pallid mice was analysed using an untargeted, liquid chromatography-coupled mass spectrometric approach...

Attempts have been made to reduce the total scan time in multi-dimensional J-resolved spectroscopic imaging (JRESI) using an echo-planar (EP) readout gradient, but acquisition duration remains a limitation for routine clinical use in the brain. We present here a significant acceleration achieved with a 4D EP-JRESI sequence that collects dual phase encoded lines within a single repetition time (TR) using two bipolar read-out trains. The performance and reliability of this novel 4D sequence, called Multi-Echo based Echo-Planar J-resolved Spectroscopic Imaging (ME-EP-JRESI), was evaluated in 10 healthy controls and a brain phantom using a 3 T MRI/MRS scanner...

Activation of presynaptic group II metabotropic glutamate receptors (mGluR2/3) inhibits drug reward and drug-seeking behavior, but the role of N-acetylaspartylglutamate (NAAG), an agonist of endogenous mGluR2/3, in heroin reward and heroin-seeking behavior remained unclear. Here, we aimed to explore the effects of exogenous NAAG on heroin self-administration and heroin-seeking behavior. First, rats were trained to self-administer heroin under a fixed ratio 1 (FR1) schedule for 10 days, then received NAAG (50 or 100 μg/10 μL in each nostril) in the absence or presence of LY341495 (1 mg/kg, i...

The main objective of this study was to utilize high field (7T) in vivo proton magnetic resonance imaging to increase the ability to detect metabolite changes in people with ALS, specifically, to quantify levels of glutamine and glutamine separately. The second objective of this study was to correlate metabolic markers with clinical outcomes of disease progression. 13 ALS participants and 12 age-matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR spectra were acquired from the left precentral gyrus using a very short echo time (TE = 5 ms) STEAM sequence...

The concentrations of fourteen neurochemicals associated with metabolism, neurotransmission, antioxidant capacity, and cellular structure were measured noninvasively from two distinct brain regions using (1)H magnetic resonance spectroscopy. Seventeen young adults (age 19-22years) and sixteen cognitively normal older adults (age 70-88years) were scanned. To increase sensitivity and specificity, (1)H magnetic resonance spectra were obtained at the ultra-high field of 7T and at ultra-short echo time. The concentrations of neurochemicals were determined using water as an internal reference and accounting for gray matter, white matter, and cerebrospinal fluid content of the volume of interest...

It has previously been shown that the HERMES method ('Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy') can be used to simultaneously edit pairs of metabolites (such as N-acetyl-aspartate (NAA) and N-acetyl aspartyl glutamate (NAAG), or glutathione and GABA). In this study, HERMES is extended for the simultaneous editing of three overlapping signals, and illustrated for the example of NAA, NAAG and Aspartate (Asp). Density-matrix simulations were performed in order to optimize the HERMES sequence...

N-acetylaspartylglutamate (NAAG) is the third most prevalent and widely distributed neurotransmitter in the mammalian nervous system. NAAG activates a group II metabotropic glutamate receptor (mGluR3) and is inactivated by an extracellular enzyme, glutamate carboxypeptidase II (GCPII) in vivo. Inhibitors of this enzyme are analgesic in animal models of inflammatory, neuropathic and bone cancer pain. NAAG and GCPII are present in the locus coeruleus, a center for the descending noradrenergic inhibitory pain system...

BACKGROUND: Lipids play an important role in maintaining the cell membrane integrity. Lipid profile is a panel of blood tests that serve as an initial medical screening for abnormalities in lipids and approximate risk for cancer, cardiovascular diseases, pancreatitis, etc., The present study evaluates the alterations in lipid profile in cancer patients, smokers, and nonsmokers and aims to achieve a correlation between them. MATERIALS AND METHODS: The study is an in vitro type of cross-sectional study with 25 oral cancer patients, 25 chronic smokers (habit persisting for 15 years or more), and 15 nonsmokers as control group...

Tissue non-specific alkaline phosphatase (TNAP) is a key player of bone mineralization and TNAP gene (ALPL) mutations in human are responsible for hypophosphatasia (HPP), a rare heritable disease affecting the mineralization of bones and teeth. Moreover, TNAP is also expressed by brain cells and the severe forms of HPP are associated with neurological disorders, including epilepsy and brain morphological anomalies. However, TNAP's role in the nervous system remains poorly understood. To investigate its neuronal functions, we aimed to identify without any a priori the metabolites regulated by TNAP in the nervous tissue...

Magnetic resonance spectroscopic imaging (MRSI) is a promising technique for mapping the spatial distribution of multiple metabolites in the human brain. These metabolite maps can be used as a diagnostic tool to gain insight into several biochemical processes and diseases in the brain. In comparison to lower field strengths, MRSI at ultra-high field strengths benefits from a higher signal to noise ratio (SNR) as well as higher chemical shift dispersion, and hence spectral resolution. This study combines the benefits of an ultra-high field magnet with the advantages of an ultra-short TE and TR single-slice FID-MRSI sequence (such as negligible J-evolution and loss of SNR due to T2 relaxation effects) and presents the first metabolite maps acquired at 9...

Brain activation studies in humans have shown the dynamic nature of neuronal N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) based on changes in their MRS signals in response to stimulation. These studies demonstrated that upon visual stimulation there was a focal increase in cerebral blood flow (CBF) and a decrease in NAA or in the total of NAA and NAAG signals in the visual cortex, and that these changes were reversed upon cessation of stimulation. In the present study we have developed an animal model in order to explore the relationships between brain stimulation, neuronal activity, CBF and NAA...